Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang, P.R. China.
Med Sci Monit. 2012 Aug;18(8):BR309-314. doi: 10.12659/msm.883263.
MicroRNAs (miRNAs) are noncoding RNAs of 18-25 nucleotides that post-transcriptionally regulate gene expression and are involved in a wide range of physiological and pathological conditions. The β-adrenergic signaling pathway plays a fundamental role in regulation of heart function. The present study was designed to investigate the expression profile of miRNAs and functional implications under conditions of β-adrenoceptor activation or inhibition in rat heart.
MATERIAL/METHODS: Hemodynamic parameters were measured to assess heart function in Wistar rats treated with isoproterenol (ISO) or propranolol (PRO). miRNA expression was analyzed by miRNA Microarray and confirmed by real-time quantitative reverse transcription PCR (real-time qRT-PCR).
Isoproterenol (ISO, a β-adrenoceptor activator) and propranolol (PRO, a β-adrenoceptor inhibitor) induced differential miRNA expression profiles. Out of 349 miRNAs measured, 43 were upregulated and nine downregulated in the ISO group, while five miRNAs were upregulated and 28 downregulated in PRO group. Among these altered miRNAs in both PRO and ISO groups, 11 were cardiac abundant and 11 showed opposite profiles between the PRO and ISO groups. The recognized anti-hypertrophic miRNAs miR-1, miR-21 and miR-27b, and the pro-hypertrophic miRNAs miR-22, miR-24, miR-199a, miR-212 and miR-214, were upregulated in the ISO group. In the PRO group, pro-hypertrophic miRNA miR-30c was upregulated, whereas miR-212 was downregulated.
β-adrenoceptor intervention alters miRNA expression profile, and miRNAs may be involved in the β-adrenoceptor signaling pathway. Cardiomyocyte hypertrophy is a balanced process between pro-hypertrophic and anti-hypertrophic regulation and involves, at the very least, miRNA participation.
微小 RNA(miRNA)是 18-25 个核苷酸的非编码 RNA,可在后转录水平上调节基因表达,参与广泛的生理和病理条件。β-肾上腺素能信号通路在调节心脏功能方面起着至关重要的作用。本研究旨在研究在β-肾上腺素受体激活或抑制的情况下,大鼠心脏中 miRNA 的表达谱及其功能意义。
材料/方法:用异丙肾上腺素(ISO)或普萘洛尔(PRO)处理 Wistar 大鼠,测量血流动力学参数以评估心脏功能。通过 miRNA 微阵列分析 miRNA 表达,并通过实时定量逆转录 PCR(实时 qRT-PCR)进行验证。
异丙肾上腺素(ISO,β-肾上腺素受体激动剂)和普萘洛尔(PRO,β-肾上腺素受体抑制剂)诱导了差异的 miRNA 表达谱。在测量的 349 个 miRNA 中,ISO 组有 43 个上调和 9 个下调,PRO 组有 5 个上调和 28 个下调。在 PRO 和 ISO 组均发生改变的这些 miRNA 中,有 11 个是心脏丰富的,有 11 个在 PRO 和 ISO 组之间呈现相反的模式。公认的抗肥厚 miRNA miR-1、miR-21 和 miR-27b,以及促肥厚 miRNA miR-22、miR-24、miR-199a、miR-212 和 miR-214,在 ISO 组中上调。在 PRO 组中,促肥厚 miRNA miR-30c 上调,而 miR-212 下调。
β-肾上腺素受体干预改变了 miRNA 表达谱,miRNA 可能参与了β-肾上腺素能信号通路。心肌肥厚是促肥厚和抗肥厚调节之间的平衡过程,至少涉及 miRNA 的参与。